Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers

Abstract

These results suggest that OATP2B1 plays an important role in the stereoselective pharmacokinetics of fexofenadine and that one-time apple juice ingestion probably inhibits intestinal OATP2B1-mediated transport of both enantiomers. In addition, this study demonstrates that the OATP2B1 inhibition effect does not require repeated ingestion or a large volume of apple juice.

The change of pharmacokinetics of fexofenadine enantiomers through the single and simultaneous grapefruit juice ingestion

“…Additionally, a previous clinical study found that a single ingestion of AJ significantly decreases the AUC 0e24 for (R)-and (S)-fexofenadine by 49% and 59%, respectively [31], while the present single-intake GFJ study showed that the AUC 0e24 values of (R)-and (S)-fexofenadine decreased by 39% and 52%, respectively (Table 1). A recent in vitro study reported that co-incubation with AJ reduces *P < 0.05, **P < 0.01, ***P < 0.001, between control phase and GFJ phase.…”

“…In our recent in vitro study [31], uptake into oocytes injected with OATP2B1 cRNA was higher for (R)-fexofenadine than (S)-fexofenadine. Consistent with these results, the present in vivo analysis demonstrated that the plasma concentration of (R)-fexofenadine was higher than the corresponding (S)-enantiomer during the control phase (Fig.…”

“…In an in vitro uptake study, the uptake of both fexofenadine enantiomers into oocytes injected with OATP2B1 cRNA is significantly higher than that into oocytes injected with water, and this effect is greater for (R)-fexofenadine [31]. In addition, AJ significantly decreases the uptake of both enantiomers into oocytes injected with OATP2B1 cRNA [31].…”

“…In an in vitro uptake study, the uptake of both fexofenadine enantiomers into oocytes injected with OATP2B1 cRNA is significantly higher than that into oocytes injected with water, and this effect is greater for (R)-fexofenadine [31]. In addition, AJ significantly decreases the uptake of both enantiomers into oocytes injected with OATP2B1 cRNA [31]. Furthermore, we have shown that the uptake of both enantiomers is the same in P-gp-, OATP1B3-, OAT3-, and multidrug and toxic compound extrusion 1 (MATE1)-expressing cells [30].…”

“…Moreover, our most recent study indicated that apple juice (AJ) significantly decreases the oral bioavailability of both fexofenadine enantiomers [31]. In an in vitro uptake study, the uptake of both fexofenadine enantiomers into oocytes injected with OATP2B1 cRNA is significantly higher than that into oocytes injected with water, and this effect is greater for (R)-fexofenadine [31].…”